Neurocomputational mechanisms of explore-exploit decision making in prefrontal and motivational neural circuits

项目摘要 探索-利用困境指的是决定何时放弃与已知的选择的挑战 探索新的机会并更多地了解它们的后果。管理这种权衡是一个基本的 行为灵活性的组成部分。过度的探索或开发阻碍学习，导致贫穷。 选择导致不想要的结果。探索-剥削决策在精神病学中研究不足，尽管 它在理解以僵化行为为特征的障碍方面的生态有效性和相关性。其中一个原因 因为我们还没有确定大脑是否编码了与管理探索-利用权衡相关的信息 不同的是，当探索的动机是由胃口或厌恶的后果。另一个原因是 虽然在人类身上有证据表明，额叶皮质-前额叶皮质最前面的部分， 灵长类独有的--执行探索新机会的决定，这是潜在的神经机制 促使探索的额极层活动的变化尚不清楚。眼眶前额叶皮质的神经元， 杏仁基底外侧核和伏隔核编码的价值信号告知探索-开发决策。这 这表明，在探索过程中，额叶皮质和动机脑区之间存在更动态的相互作用。 利用比目前假设更多的决策。这一提议检验了额叶大脑皮层的假设 实施探索的决策，但依赖于在动机中计算的欲望和厌恶的价值信号 平衡探索和开发的神经回路。我们预测自下而上反馈到额叶大脑皮层 来自大脑中与信号有关的区域奖赏价值对于平衡探索和 剥削。在目标1中，我们将测试猴子在多臂匪徒任务中的选择是否更频繁 与收益或损失相关联，并使用选择的计算模型来定义价态依赖 他们探索的意愿存在差异。在目标2中，我们将同时记录额叶皮质的神经活动 以及眶前叶皮质、杏仁基底外侧核和伏隔核，以确定自下而上的信息 从激励性大脑区域流向额叶皮质可以预测探索或利用的决定，如果 当勘探的动机是收益还是损失时，勘探选择的编码是不同的。在Aim 3中将 使用通路特异性化学遗传学兴奋或抑制投射到核团的杏仁核基底外侧神经元 伏隔核，同时记录伏隔核和额叶皮质的神经活动。我们将测试一下 预测由于剥削信号的高度编码，该途径的激发增加了剥削 伏核和额叶皮质探测信号的编码减少。在完成后 这些目的，我们将了解如何在探索-剥削决策不平衡出现在不同的精神病学家 以前额叶皮质和动机回路的完整性为基础的障碍。

Project Summary The explore-exploit dilemma refers to the challenge of deciding when to forego choices with known consequences to explore new opportunities and learn more about them. Managing this trade-off is a fundamental component of behavioral flexibility. Excessive exploration or exploitation impedes learning and results in poor choices leading to undesired outcomes. Explore-exploit decision making is understudied in psychiatry despite its ecological validity and relevance in understanding disorders characterized by inflexible behaviors. One reason for this is we have not identified if the brain encodes information relevant for managing explore-exploit tradeoffs differently when exploration is motivated by either appetitive or aversive consequences. Another reason is that while there is evidence in humans that frontopolar cortex—the most anterior part of prefrontal cortex which is unique to primates—implements decisions to explore new opportunities, the neural mechanisms underlying changes in frontopolar activity that prompt exploration are unclear. Neurons in the orbitofrontal cortex, basolateral amygdala, and nucleus accumbens encode value signals that inform explore-exploit decisions. This suggests a more dynamic interplay between frontopolar cortex and motivational brain regions during explore- exploit decision making than is currently hypothesized. This proposal tests the hypothesis that frontopolar cortex implements decisions to explore, but is reliant on appetitive and aversive value signals computed in motivational neural circuits to balance exploration and exploitation. We predict that bottom-up feedback to frontopolar cortex from brain regions classically associated with signaling reward value is critical for balancing exploration and exploitation. In Aim 1 we will test if monkeys explore more often when choices in a multi-arm bandit task are associated with gains or losses, and use computational modeling of choices to define valence dependent differences in their willingness to explore. In Aim 2 we will simultaneously record neural activity in frontopolar and orbitofrontal cortex, basolateral amygdala, and nucleus accumbens to determine if bottom-up information flow from motivational brain regions to frontopolar cortex predicts decisions to explore or exploit, and if exploratory choices are encoded differently when exploration is motivated by gains versus losses. In Aim 3 will use pathway-specific chemogenetics to excite or inhibit basolateral amygdala neurons that project to the nucleus accumbens, while recording neural activity in the nucleus accumbens and frontopolar cortex. We will to test the prediction that excitation of this pathway increases exploitation due to heightened encoding of exploitative signals in nucleus accumbens and decreased encoding of exploration signals in frontopolar cortex. Upon completion of these aims, we will understand how imbalances in explore-exploit decision making emerge in different psychiatric disorders based on the integrity of prefrontal cortex and motivational circuits.